C. Boutros1,2, M. Bedra2, J. Emel2, O. Ioffe3, N. Hanna1, N. Espat4, S. Katz4 1University Of Maryland School Of Medicine,Surgery,Baltimore, MD, USA 2University Of Maryland Baltimore Washington Medical Center,Tate Cancer Center,Glen Burnie, MD, USA 3University Of Maryland School Of Medicine,Pathology,Baltimore, MD, USA 4Roger Williams Medical Center,Surgery,Providence, RI, USA
Introduction: Tumor infiltrating lymphocytes (TIL) are independent predictors of survival for numerous metastatic solid tumors. The biologic significance of TIL in pseudomyxoma peritonei (PMP) has yet to be elucidated.
Methods: We accessed our tissue bank for surgical patients after cytoreductive surgery and heated chemotherapy for PMP. Immunohistochemical staining (IHC)for CD3, CD4, CD8 and FOXP3 was correlated with clinicopathologic factors including preoperative CEA and PCI. Markers were correlated with survival using the median cell count as the cutoff point for LOW and HIGH groups.
Results: Of 50 patients, 31 had suitable tissue for IHC analysis. The mean age was 59, preoperative CEA 44.0 and PCI score 17. Median survival was 45 months. CD3, CD4, and CD8 density did not correlate with patient survival. Similarly, preoperative CEA or PCI score alone were not significant predictors of survival. FOXP3, a marker of suppressive regulatory T cells (Treg), was a strong predictor of 5-year survival (82% FOXP3LOW vs 28% FOXP3HI , p=0.001). FOXP3/CD4 ratio predicted of 30 and 60-month survival (80.5% for LOW vs 31% for HIGH, p=0.038 at 30 months, p=0.004 at 60 months). Similarly, FOXP3/CD8 ratio was found to be a predictor of 60 months survival (77% for LOW, vs 33% for HIGH;p=0.023). Low CD8/CD4 ratio correlated with high preoperative CEA and high PCI score (p=0.01). Patients with the combination of low CEA, low PCI score, and high CD8/CD4 ratio had longer survival times (p=0.01 )
Conclusion: TIL proved to be significant predictors of outcome in this small group of patients. A high number of tumor infiltrating suppressive FOXP3+ Treg predicted shorter survival time, suggesting that immunotherapeutic approaches may benefit PMP-PC patients.